Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches.


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All studies must disclose on these points even when the disclosure is negative.This retrospective study is a gender-based analysis.Gender information was collected from medical record and used as a main variable for multivariate adjustment and subgroup analysis.
The retrospective study contains race and ethnicity information, which are used as main factor in our multivariate adjustment.
The details of population are presented in Table 1 The patients were obtained from in-house MD Anderson databased as well as public datasets MD Anderson IRB approval was obtained no sample size calculation.We applied strict patient inclusion criteria as shown in Figure 1.The robust performance of habitat imaging subtypes were demonstrated in discovery and validation sets (Figure 4) as well as univariate and multivariate analyses (Table 3 and Table 4) the detailed exclusions for each cohort were presented in Figure 1.We excluded patients without PET/CT scans, stage IV disease, without follow up information.
we have four independent cohorts (figure 1).The subtypes were identified in discovery cohorts, and further validated in MD Anderson testing set as well as the ACRIN trial set.
This is a multicenter retrospective study without randomization.Two cohorts were used for discovery purpose, and two independent cohorts for validation (Figure 1).Describe the methods by which all novel plant genotypes were produced.This includes those generated by transgenic approaches, gene editing, chemical/radiation-based mutagenesis and hybridization.For transgenic lines, describe the transformation method, the number of independent lines analyzed and the generation upon which experiments were performed.For gene-edited lines, describe the editor used, the endogenous sequence targeted for editing, the targeting guide RNA sequence (if applicable) and how the editor was applied.was applied.was applied.
Report on the source of all seed stocks or other plant material used.
This is a retrospective study.During model development and validation, the clinical outcome data were blinded to assess the clinical values of habitat NSCLC+Radiogenomics#28672347d6e83195f69f438ca0d1a3d20fbc450d.The raw FDG-PET/CT and clinical data of ACRIN 6668/RTOG 0235 cohort are publicly available on The Cancer Imaging Archive https://wiki.cancerimagingarchive.net/pages/viewpage.action?pageId=39879162#398791626e061ab3228446d59c8ce2ac2d1aa117 .The raw FDG-PET/CT of ICON and PROSPECT are not publicly shared to protect patient privacy, but are available for research use from the corresponding author.MTA is required to be approved by MD Anderson committees by providing the research plan and is restricted to non-commercial academic research purposes.Request can be submitted to J.W. and will receive an internal review response within 30 days.In addition, anonymized data and the input for the predictive models are available at Zenodo https://doi.org/10.5281/zenodo.1061153659.Deidentified ctDNA data for patients in the internal validation cohort are available in Source data for Fig 6.The genomics data of PROSPECT cohort are available at GEO repository GSE42127 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42127.The genomics data of TCIA cohort are available at GEO repository GSE103584 https:// www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103584.The genomics data of ICON cohort are available at [UPLOADING IT NOW].The remaining data are available within the Article, Source Data, Supplementary Information, and Supplementary Data files.Source data are provided with this paper.
If applicable, state the seed stock centre and catalogue number.If plant specimens were collected from the field, describe the collection location, date and sampling procedures.Describe any authentication procedures for each seed stock used or novel genotype generated.Describe any experiments used to Describe any authentication procedures for each seed stock used or novel genotype generated.Describe any experiments used to Describe any authentication procedures for each seed stock used or novel genotype generated.Describe any experiments used to assess the effect of a mutation and, where applicable, how potential secondary effects (e.g.second site T-DNA insertions, mosiacism, off-target gene editing) were examined.